JP2713384B2 - Use of 2-amino-6- (trifluoromethoxy) -benzothiazole (riluzole) for obtaining a medicament intended for the treatment of motor neuron disease - Google Patents

Use of 2-amino-6- (trifluoromethoxy) -benzothiazole (riluzole) for obtaining a medicament intended for the treatment of motor neuron disease

Info

Publication number
JP2713384B2
JP2713384B2 JP5515371A JP51537193A JP2713384B2 JP 2713384 B2 JP2713384 B2 JP 2713384B2 JP 5515371 A JP5515371 A JP 5515371A JP 51537193 A JP51537193 A JP 51537193A JP 2713384 B2 JP2713384 B2 JP 2713384B2
Authority
JP
Japan
Prior art keywords
amino
benzothiazole
trifluoromethoxy
lateral sclerosis
amyotrophic lateral
Prior art date
Legal status (The legal status is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the status listed.)
Expired - Lifetime
Application number
JP5515371A
Other languages
Japanese (ja)
Other versions
JPH07504655A (en
Inventor
ルーベル，エリク
Original Assignee
ローン−プーラン・ロレ・ソシエテ・アノニム
Priority date (The priority date is an assumption and is not a legal conclusion. Google has not performed a legal analysis and makes no representation as to the accuracy of the date listed.)
Filing date
Publication date
Family has litigation
First worldwide family litigation filed litigation Critical https://patents.darts-ip.com/?family=9427427&utm_source=google_patent&utm_medium=platform_link&utm_campaign=public_patent_search&patent=JP2713384(B2) "Global patent litigation dataset” by Darts-ip is licensed under a Creative Commons Attribution 4.0 International License.
Application filed by ローン−プーラン・ロレ・ソシエテ・アノニム filed Critical ローン−プーラン・ロレ・ソシエテ・アノニム
Publication of JPH07504655A publication Critical patent/JPH07504655A/en
Application granted granted Critical
Publication of JP2713384B2 publication Critical patent/JP2713384B2/en
Anticipated expiration legal-status Critical
Expired - Lifetime legal-status Critical Current

Links

Classifications

    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61K—PREPARATIONS FOR MEDICAL, DENTAL OR TOILETRY PURPOSES
    • A61K31/00—Medicinal preparations containing organic active ingredients
    • A61K31/33—Heterocyclic compounds
    • A61K31/395—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins
    • A61K31/41—Heterocyclic compounds having nitrogen as a ring hetero atom, e.g. guanethidine or rifamycins having five-membered rings with two or more ring hetero atoms, at least one of which being nitrogen, e.g. tetrazole
    • A61K31/425—Thiazoles
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P21/00—Drugs for disorders of the muscular or neuromuscular system
    • A61P21/02—Muscle relaxants, e.g. for tetanus or cramps
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P25/00—Drugs for disorders of the nervous system
    • A61P25/28—Drugs for disorders of the nervous system for treating neurodegenerative disorders of the central nervous system, e.g. nootropic agents, cognition enhancers, drugs for treating Alzheimer's disease or other forms of dementia
    • A—HUMAN NECESSITIES
    • A61—MEDICAL OR VETERINARY SCIENCE; HYGIENE
    • A61P—SPECIFIC THERAPEUTIC ACTIVITY OF CHEMICAL COMPOUNDS OR MEDICINAL PREPARATIONS
    • A61P9/00—Drugs for disorders of the cardiovascular system
    • A61P9/10—Drugs for disorders of the cardiovascular system for treating ischaemic or atherosclerotic diseases, e.g. antianginal drugs, coronary vasodilators, drugs for myocardial infarction, retinopathy, cerebrovascula insufficiency, renal arteriosclerosis

Landscapes

  • Health & Medical Sciences (AREA)
  • Pharmacology & Pharmacy (AREA)
  • Veterinary Medicine (AREA)
  • Public Health (AREA)
  • General Health & Medical Sciences (AREA)
  • Animal Behavior & Ethology (AREA)
  • Chemical & Material Sciences (AREA)
  • Life Sciences & Earth Sciences (AREA)
  • Medicinal Chemistry (AREA)
  • Engineering & Computer Science (AREA)
  • Bioinformatics & Cheminformatics (AREA)
  • Chemical Kinetics & Catalysis (AREA)
  • Neurology (AREA)
  • Nuclear Medicine, Radiotherapy & Molecular Imaging (AREA)
  • General Chemical & Material Sciences (AREA)
  • Organic Chemistry (AREA)
  • Epidemiology (AREA)
  • Neurosurgery (AREA)
  • Orthopedic Medicine & Surgery (AREA)
  • Biomedical Technology (AREA)
  • Physical Education & Sports Medicine (AREA)
  • Vascular Medicine (AREA)
  • Cardiology (AREA)
  • Psychiatry (AREA)
  • Urology & Nephrology (AREA)
  • Hospice & Palliative Care (AREA)
  • Pain & Pain Management (AREA)
  • Heart & Thoracic Surgery (AREA)
  • Pharmaceuticals Containing Other Organic And Inorganic Compounds (AREA)
  • Thiazole And Isothizaole Compounds (AREA)
  • Surgical Instruments (AREA)
  • Percussion Or Vibration Massage (AREA)
  • Medicinal Preparation (AREA)

Abstract

Use of 2-amino-6-(trifluoromethoxy)benzothiazole or a salt of this compound with a pharmaceutically acceptable acid for the manufacture of a medicament for the treatment of motor neuron diseases, especially amyotrophic lateral sclerosis and, in particular, amyotrophic lateral sclerosis of bulbar onset or of the bulbar type.

Description

【発明の詳細な説明】 本発明は、２−アミノ−６−トリフルオロメトキシベ
ンゾチアゾールまたはこの化合物と医薬として受容し得
る酸との塩の、運動ニューロン疾患、特に筋萎縮性側索
硬化症、特に早期延髄障害または延髄形状の疾病を伴う
筋萎縮性側索硬化症の処置を意図した医薬を得るための
使用に関するものである。DETAILED DESCRIPTION OF THE INVENTION The present invention relates to the use of 2-amino-6-trifluoromethoxybenzothiazole or a salt of this compound with a pharmaceutically acceptable acid, for motor neuron disease, in particular amyotrophic lateral sclerosis, In particular, it relates to the use for obtaining a medicament intended for the treatment of amyotrophic lateral sclerosis with early medullary disorders or medullary shaped diseases.

２−アミノ−６−（トリフルオロメトキシ）−ベンゾ
チアゾール（国際非独占名称：リルゾール（riluzol
e））は、抗てんかん薬、穏和安定薬および睡眠薬とし
て（特許EP50,551）、精神分裂症の処置に（EP305,27
6）、睡眠障害および鬱病の処置に（EP305,277）、脳血
管障害の処置に、ならびに麻酔薬として（EP282,971）
有用であることが知られている。2-amino-6- (trifluoromethoxy) -benzothiazole (International non-exclusive name: riluzol
e)) as antiepileptic, mild stabilizing and sleeping pills (patent EP50,551) for the treatment of schizophrenia (EP305,27)
6), for the treatment of sleep disorders and depression (EP305,277), for the treatment of cerebrovascular disorders and as an anesthetic (EP282,971)
It is known to be useful.

２−アミノ−６−トリフルオロメトキシベンゾチアゾ
ール、またはこの化合物と医薬として受容し得る酸との
塩が運動ニューロン疾患、特に筋萎縮性側索硬化症、特
に早期延髄障害または延髄形状の疾病を伴う筋萎縮性側
索硬化症の処置に有用であることが、ここに見いだされ
た。2-Amino-6-trifluoromethoxybenzothiazole, or a salt of this compound with a pharmaceutically acceptable acid, is associated with motor neuron disease, especially amyotrophic lateral sclerosis, especially early medulla impairment or medulla shaped disease It has now been found to be useful in the treatment of amyotrophic lateral sclerosis.

この使用はヒトにおいて、偽薬に対する二重盲検研究
で測定された：運動ニューロン疾病に、特に筋萎縮性側
索硬化症に悩む77人の患者を２×50mg/日のリルゾール
の経口投与（50mgの投与薬剤を含有する錠剤）により12
ないし18ケ月間処置し、78人の患者には偽薬を投与し
た。This use was measured in humans in a double-blind study on placebo: 77 patients suffering from motor neuron disease, especially amyotrophic lateral sclerosis, were given 2 × 50 mg / day of riluzole orally (50 mg Tablets containing the drug to be administered)
And treated for 18 months and 78 patients received placebo.

得られた結果を研究中の生存に関して分析するが、
“研究脱落者”（研究からの逸脱者）には実際に死亡し
た個体も、その臨床状況が気管切開または補助換気への
移動を必要とする個体も含まれるものと理解する。The results obtained are analyzed for survival during the study,
It is understood that “student dropouts” (departures from the study) include individuals who have actually died, as well as those whose clinical situation requires tracheostomy or transfer to assisted ventilation.

この研究において、偽薬を投与された患者の51％が死
亡するが、リルゾールを投与された患者ではこの百分率
は44％に低下する（ウィルコキソン（Wilcoxon）試験プ
レンティス（R.L.PRENTICE），ビオメトリカ（Biometri
ka）,65,167−179（1978）における確率は0.018に等し
く、また成層ログランク試験（ペト（R.PETO）およびペ
ト（J.PETO），王立統計協会誌（Journal of RoyalStat
istical Society），シリーズA,135巻,185−207（197
2）における確率は0.06に等しい）。In this study, 51% of patients receiving placebo died, but this percentage dropped to 44% in patients receiving riluzole (Wilcoxon trial Prentis, RLPRENTICE, Biometrica).
ka), 65, 167-179 (1978), with a probability equal to 0.018, a stratified log-rank test (R. PETO and R. PETO), and the Journal of RoyalStat
istical Society), Series A, 135, 185-207 (197
The probability in 2) is equal to 0.06).

早期延髄障害または延髄形状の疾患を伴う筋萎縮性側
索硬化症（最も深刻な形状の疾患；この型の患者の通常
の平均生存は３年未満である）に悩む対象者では、偽薬
を投与された患者の65％が死亡するが、リルゾールを投
与された患者ではこの百分率は47％に低下する（ウィル
コキソン試験における確率は0.011に等しく、またログ
ランク試験（ペトおよびペト，王立統計協会誌，シリー
ズA,135巻,185−207（1972）における確率は0.032に等
しい）。Administer placebo in subjects afflicted with amyotrophic lateral sclerosis with early medullary disorders or medulla-shaped disease (the most severe form of the disease; the normal average survival of patients with this type is less than 3 years) 65% of patients who died have a riluzole dose, but this percentage drops to 47% (probability in the Wilcoxon test is equal to 0.011, and log-rank test (Pet and Pet, Royal Statistical Society) , Series A, Volume 135, 185-207 (1972) has a probability equal to 0.032.)

したがって、２−アミノ−６−（トリフルオロメトキ
シ）−ベンゾチアゾールは統計的に有意な様式で運動ニ
ューロン疾患、特に筋萎縮性側索硬化症に悩む患者の生
存率を増加させ、この効果は早期延髄障害または延髄形
状の疾患を伴う筋萎縮性側索硬化症に悩む患者において
特に顕著である。Thus, 2-amino-6- (trifluoromethoxy) -benzothiazole increases the survival rate of patients suffering from motor neuron disease, especially amyotrophic lateral sclerosis, in a statistically significant manner, and this effect is premature. This is especially true in patients suffering from amyotrophic lateral sclerosis with medullary disorders or medullary shaped diseases.

２−アミノ−６−（トリフルオロメトキシ）−ベンゾ
チアゾールは、特許EP50,551に記載されている方法に従
って製造することができる。2-Amino-6- (trifluoromethoxy) -benzothiazole can be prepared according to the method described in patent EP 50,551.

医薬として受容し得る塩としては、無機酸との付加
塩、たとえば塩酸塩、硫酸塩、硝酸塩およびリン酸塩、
もしくは有機酸酸との塩、たとえば酢酸塩、プロピオン
酸塩、コハク酸塩、シュウ酸塩、安息香酸塩、フマル酸
塩、マレイン酸塩、メタンスルホン酸塩、イセチオン酸
塩、テオフィリン酢酸塩、サリチル酸塩、フェノールフ
タリン酸塩およびメチレンビス−（β−ヒドロキシナフ
トエ酸）塩、または、これらの誘導体の置換誘導体を特
に挙げることができる。Pharmaceutically acceptable salts include addition salts with inorganic acids, such as hydrochlorides, sulfates, nitrates and phosphates,
Or salts with organic acids such as acetate, propionate, succinate, oxalate, benzoate, fumarate, maleate, methanesulfonate, isethionate, theophylline acetate, salicylic acid Mention may in particular be made of salts, phenol phthalates and methylene bis- (β-hydroxynaphthoic acid) salts or substituted derivatives of these derivatives.

本発明記載の医薬は、遊離の形状の、または医薬とし
て受容し得る酸との付加塩の形状の、純粋な状態の、ま
たは医薬として混和可能な、不活性であっても生理学的
に活性であってもよい他のいずれかの生成物と混和した
組成物の形状の、２−アミノ−６−（トリフルオロメト
キシ）−ベンゾチアゾールよりなるものである。本発明
記載の医薬は経口的に、非経口的に、直腸に、または局
所的に使用することができる。The medicament according to the invention may be in an inactive or physiologically active form, either in free form or in the form of an addition salt with a pharmaceutically acceptable acid, in pure form or as a pharmaceutically compatible compound. Consisting of 2-amino-6- (trifluoromethoxy) -benzothiazole in the form of a composition admixed with any other product that may be present. The medicament according to the invention can be used orally, parenterally, rectally or topically.

経口投与用の固体組成物としては錠剤、丸薬、粉末
（ゼラチンカプセル、ウェーファーカプセル）または顆
粒を使用することができる。これらの組成物において
は、本発明記載の活性要素を１種または２種以上の不活
性希釈剤、たとえば澱粉、セルローズ、ショ糖、乳糖ま
たはシリカと、アルゴン気流下で混合する。これらの組
成物はまた、希釈剤以外の物質、たとえば１種または２
種以上の潤滑剤、たとえばステアリン酸マグネシウムも
しくはタルク、着色剤、被覆剤（糖衣錠）またはワニス
を含んでいてもよい。As the solid composition for oral administration, tablets, pills, powders (gelatin capsules, wafer capsules) or granules can be used. In these compositions, the active ingredient according to the invention is mixed with one or more inert diluents, for example starch, cellulose, sucrose, lactose or silica, under a stream of argon. These compositions may also contain substances other than diluents, for example one or two.
It may also contain one or more lubricants, such as magnesium stearate or talc, coloring agents, coatings (dragees) or varnishes.

経口投与用の液体組成物としては、不活性希釈剤、た
とえば水、エタノール、グリセロール、植物油または液
体パラフィンを含有する医薬として受容し得る溶液、懸
濁液、乳濁液、シロップまたはエリキシルを使用するこ
とができる。これらの組成物は、希釈剤以外の物質、た
とえば湿潤剤、甘味料、濃化剤、風味剤または安定化用
の生成物を含んでいてもよい。As liquid compositions for oral administration, use is made of a pharmaceutically acceptable solution, suspension, emulsion, syrup or elixir containing an inert diluent such as water, ethanol, glycerol, vegetable oil or liquid paraffin. be able to. These compositions may contain substances other than diluents, for example, wetting agents, sweetening agents, thickening agents, flavoring agents or stabilizing products.

非経口投与用の滅菌組成物には、好ましいものとして
溶液、水性または非水性の懸濁液または乳濁液が可能で
ある。溶媒またはビークルとしては、水、プロピレング
リコール、ポリエチレングリコール、植物油特にオリー
ブ油、注射可能な有機エステルたとえばオレイン酸エチ
ル、等の適当な有機溶媒を使用することができる。これ
らの組成物はまた補剤、特に湿潤剤、等張剤、乳化剤、
分散剤および安定剤を含有することもできる。滅菌は数
週間にわたって、たとえば無菌濾過により、組成物への
滅菌剤の組み入れにより、照射により、または加熱によ
り実行することができる。これらはまた、使用時に滅菌
水に、または他のいずれかの注射可能な滅菌媒体に溶解
させ得る滅菌固体組成物の形状で製造することもでき
る。Sterile compositions for parenteral administration can preferably be solutions, aqueous or non-aqueous suspensions or emulsions. As the solvent or vehicle, a suitable organic solvent such as water, propylene glycol, polyethylene glycol, vegetable oil, especially olive oil, or an injectable organic ester such as ethyl oleate can be used. These compositions may also contain adjuvants, especially wetting agents, isotonic agents, emulsifiers,
Dispersants and stabilizers can also be included. Sterilization can be performed over several weeks, for example, by sterile filtration, by incorporation of a sterilizing agent into the composition, by irradiation, or by heating. They can also be manufactured in the form of sterile solid compositions which can be dissolved in sterile water for use or in any other sterile injectable medium.

直腸投与用の組成物は、活性生成物以外に賦形剤たと
えばココアバター、半合成グリセリドまたはポリエチレ
ングリコールをも含有する坐薬または直腸カプセルであ
る。Compositions for rectal administration are suppositories or rectal capsules which, in addition to the active product, also contain excipients such as cocoa butter, semi-synthetic glycerides or polyethylene glycols.

局所投与用の組成物には、たとえばクリーム、ローシ
ョン、うがい薬、点鼻薬またはエアロゾルが可能であ
る。Compositions for topical administration can be, for example, creams, lotions, gargles, nasal drops or aerosols.

投与量は、目標とする効果に、処置の継続時間に、ま
た使用する投与経路に応じて異なるが；一般に、成人に
は日量50ないし400mgの活性化合物であり、単一の投与
量は25ないし200mgの範囲の活性化合物である。Dosages will vary depending on the desired effect, on the duration of the treatment and on the route of administration used; in general, for adults, a daily dose of 50 to 400 mg of the active compound is given, with a single dose of 25 mg Active compound in the range from to 200 mg.

一般的に言えば、医師は年令および体重、ならびに処
置すべき対象者に特徴的な他の全ての要因に応じて妥当
な投与量を決定する。Generally speaking, a physician will determine the appropriate dosage depending on age and weight, as well as any other factors characteristic of the subject to be treated.

以下の実施例は本発明記載の医薬を説明するものであ
る 実施例Ａ 50mgの投与量の活性生成物を含有し、以下の組成を有
する錠剤を通常の技術に従って製造する： −２−アミノ−６−（トリフルオロメトキシ）−ベンゾ
チアゾール 50mg −マンニトール 64mg −微結晶セルローズ 50mg −ポリビドン，賦形剤 12mg −カルボキシメチル澱粉ナトリウム 16mg −タルク 4mg −ステアリン酸マグネシウム 2mg −コロイド状シリカ，無水 2mg −メチルヒドロキシプロピルセルローズ、ポリエチレン グリコール6000および二酸化チタニウムの混合物（7
2:3.5:24.5） 最終的なフィルム被覆錠剤の重量を245mgにする量 実施例Ｂ 50mgの投与量の活性生成物を含有し、以下の組成を有
する硬質ゼラチンカプセルを通常の技術に従って製造す
る： −２−アミノ−６−（トリフルオロメトキシ）−ベンゾ
チアゾール 50mg −セルローズ 18mg −乳糖 55mg −コロイド状シリカ 1mg −カルボキシメチル澱粉ナトリウム 10mg −タルク 10mg −ステアリン酸マグネシウム 1mg 実施例Ｃ 10mgの活性生成物を含有し、以下の組成を有する注射
可能な溶液を製造する： −２−アミノ−６−（トリフルオロメトキシ）−ベンゾ
チアゾール 10 mg −安息香酸 80 mg −ベンジルアルコール 0.06cm3 −安息香酸ナトリウム 80 mg −エタノール,95％ 0.4 cm3 −水酸化ナトリウム 24 mg −プロピレングリコール 1.6 cm3 −水 全量を4cm3にする量The following examples illustrate the medicaments according to the invention. Example A Tablets containing a dose of 50 mg of the active product and having the following composition are prepared according to the usual techniques: -2-amino- 6- (trifluoromethoxy) -benzothiazole 50 mg-mannitol 64 mg-microcrystalline cellulose 50 mg-polyvidone, excipient 12 mg-sodium carboxymethyl starch 16 mg-talc 4 mg-magnesium stearate 2 mg-colloidal silica, anhydrous 2 mg-methylhydroxyl A mixture of propyl cellulose, polyethylene glycol 6000 and titanium dioxide (7
2: 3.5: 24.5) Amount to bring the final film-coated tablet to a weight of 245 mg. Example B A hard gelatin capsule containing the active product in a dosage of 50 mg and having the following composition is prepared according to the usual techniques: 50 mg of 2-amino-6- (trifluoromethoxy) -benzothiazole-18 mg of cellulose-55 mg of lactose-1 mg of colloidal silica-10 mg of sodium carboxymethyl starch-10 mg of talc-1 mg of magnesium stearate Example C 10 mg of the active product Produce an injectable solution containing and having the following composition: 2-amino-6- (trifluoromethoxy) -benzothiazole 10 mg-benzoic acid 80 mg-benzyl alcohol 0.06 cm 3 -sodium benzoate 80 mg - ethanol, 95% 0.4 cm 3 - sodium hydroxide 24 mg - propylene glycol 1.6 cm 3 - the amount of the total water to 4 cm 3

───────────────────────────────────────────────────── フロントページの続き (56)参考文献 特開 昭57−95910（ＪＰ，Ａ) 特開 平３−52878（ＪＰ，Ａ) 国際公開91／17984（ＷＯ，Ａ１) 国際公開91／18892（ＷＯ，Ａ１) Ｊ．Ｎｅｕｒｏｓｃｉ．，第９巻第11 号（1989）第3720−3727頁 Ｎｅｕｒｏｓｃｉ，Ｌｅｔｔ，第88巻 第２号（1988）第195−200頁 Ｎｅｕｒｏｐｈａｒｍａｃｏｌｏｇ ｙ，第24巻第８号（1985）第767−773頁 ──────────────────────────────────────────────────続 き Continuation of the front page (56) References JP-A-57-95910 (JP, A) JP-A-3-52878 (JP, A) WO 91/17984 (WO, A1) WO 91/18892 ( WO, A1) Neurosci. Vol. 9, No. 11 (1989), pp. 3720-3727 Neurosci, Lett, Vol. 88, No. 2 (1988), pp. 195-200, Neuropharmacology, Vol. 24, No. 8, (1985) pp. 767-773.

Claims (5)

(57)【特許請求の範囲】(57) [Claims] 【請求項１】２−アミノ−６−（トリフルオロメトキ
シ）−ベンゾチアゾール、またはこの化合物と医薬とし
て受容し得る酸との塩を有効成分として含んでなる、運
動ニユーロン疾患の処置のための医薬製剤。1. A medicament for the treatment of motor neuron disease, comprising as an active ingredient 2-amino-6- (trifluoromethoxy) -benzothiazole or a salt of this compound and a pharmaceutically acceptable acid. Formulation. 【請求項２】運動ニユーロン疾患が、筋萎縮性側索硬化
症である、請求の範囲１記載の医薬製剤。2. The pharmaceutical preparation according to claim 1, wherein the motor neuron disease is amyotrophic lateral sclerosis. 【請求項３】筋萎縮性側索硬化症が、早期延髄障害を伴
う筋萎縮性側索硬化症である、請求の範囲２記載の医薬
製剤。3. The pharmaceutical preparation according to claim 2, wherein the amyotrophic lateral sclerosis is amyotrophic lateral sclerosis with early medulla oblongata. 【請求項４】筋萎縮性側索硬化症が、延髄形状による筋
萎縮性側索硬化症である、請求の範囲２記載の医薬製
剤。4. The pharmaceutical preparation according to claim 2, wherein the amyotrophic lateral sclerosis is amyotrophic lateral sclerosis due to medulla oblongata. 【請求項５】25ないし200mgの２−アミノ−６−（トリ
フルオロメトキシ）−ベンゾチアゾールを含む、請求の
範囲１ないし４のいずれかに記載の医薬製剤。5. The pharmaceutical preparation according to claim 1, comprising 25 to 200 mg of 2-amino-6- (trifluoromethoxy) -benzothiazole.
JP5515371A 1992-03-06 1992-10-22 Use of 2-amino-6- (trifluoromethoxy) -benzothiazole (riluzole) for obtaining a medicament intended for the treatment of motor neuron disease Expired - Lifetime JP2713384B2 (en)

Applications Claiming Priority (3)

Application Number Priority Date Filing Date Title
FR9202696A FR2688138B1 (en) 1992-03-06 1992-03-06 APPLICATION OF AMINO-2 TRIFLUOROMETHOXY-6 BENZOTHIAZOLE TO OBTAIN A MEDICINE FOR THE TREATMENT OF AMYOTROPHIC LATERAL SCLEROSIS.
FR92/02696 1992-03-06
PCT/FR1992/000992 WO1993017683A1 (en) 1992-03-06 1992-10-22 Application of 2-amino 6-trifluoromethoxy benzothiazole (riluzole) for obtaining a drug useful in the treatment of motor neuron diseases

Publications (2)

Publication Number Publication Date
JPH07504655A JPH07504655A (en) 1995-05-25
JP2713384B2 true JP2713384B2 (en) 1998-02-16

Family

ID=9427427

Family Applications (1)

Application Number Title Priority Date Filing Date
JP5515371A Expired - Lifetime JP2713384B2 (en) 1992-03-06 1992-10-22 Use of 2-amino-6- (trifluoromethoxy) -benzothiazole (riluzole) for obtaining a medicament intended for the treatment of motor neuron disease

Country Status (22)

Country Link
US (1) US5527814A (en)
EP (2) EP0558861A1 (en)
JP (1) JP2713384B2 (en)
KR (1) KR100190296B1 (en)
AT (1) ATE149833T1 (en)
AU (1) AU666150B2 (en)
CA (1) CA2117466C (en)
CZ (1) CZ281293B6 (en)
DE (1) DE69218255T2 (en)
DK (1) DK0627919T3 (en)
ES (1) ES2098558T3 (en)
FR (1) FR2688138B1 (en)
GR (1) GR3022797T3 (en)
HU (1) HU217130B (en)
IL (1) IL103493A (en)
MX (1) MX9206109A (en)
NO (1) NO306534B1 (en)
RU (1) RU2110260C1 (en)
SK (1) SK279046B6 (en)
UA (1) UA41879C2 (en)
WO (1) WO1993017683A1 (en)
ZA (1) ZA928213B (en)

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008010315A1 (en) 2006-07-19 2008-01-24 Nippon Medical School Foundation Therapeutic agent for amyotrophic lateral sclerosis

Families Citing this family (62)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2699077B1 (en) * 1992-12-16 1995-01-13 Rhone Poulenc Rorer Sa Application of anticonvulsants in the treatment of neurological lesions linked to trauma.
FR2702148B1 (en) * 1993-03-05 1995-04-07 Rhone Poulenc Rorer Sa Application of anti-convulsants in the treatment of neuro-AIDS.
FR2714828B1 (en) * 1994-01-12 1996-02-02 Rhone Poulenc Rorer Sa Application of riluzole in the treatment of mitochondrial diseases.
UA57004C2 (en) * 1995-10-26 2003-06-16 Санофі - Сінтелябо Drug containing 1-(2-napht-2-ylethyl)-4-(3-trifluoromethylphenylo)-1,2,3,6-tetrahydropyridine (variants) and method for treating lateral amyotrophic sclerosis
FR2753379B1 (en) 1996-09-13 1998-10-30 Rhone Poulenc Rorer Sa METHOD OF TREATING AMYOTROPHIC SIDE SCLEROSIS
EP0999204B1 (en) 1997-07-25 2004-10-13 Nippon Kayaku Kabushiki Kaisha Novel compound having effect of promoting neuron differentiation
CN1290166A (en) * 1998-01-09 2001-04-04 Mor－研究应用有限公司 Treatment of Dyskinesie
US6417210B1 (en) 1998-01-09 2002-07-09 Mor-Research Applications Ltd. Treatment of dyskinesias and Parkinson's disease with riluzole and levodopa
FR2785808B1 (en) * 1998-11-13 2002-12-06 Aventis Laboratoire RILUZOLE AND ALPHA-TOCOPHEROL ASSOCIATION
DE60017733T2 (en) * 1999-06-04 2006-01-12 Vereniging Voor Christelijk Wetenschappelijk Onderwijs USE OF RILUZOL FOR THE TREATMENT OF MULTIPLE SCLEROSIS
DE60041365D1 (en) 1999-06-04 2009-02-26 Vereniging Voor Christelijk Wetenschappelijk Onderwijs Use of riluzole for the treatment of multiple sclerosis
JP2001021609A (en) * 1999-07-07 2001-01-26 Mitsubishi Electric Corp Method of inspecting semiconductor integrated circuit
DE19940524C2 (en) * 1999-08-26 2003-06-18 Karl-Heinz Lenzkes Vehicle wheel, in particular for passenger vehicles
FR2801217B1 (en) * 1999-11-24 2002-12-06 Aventis Pharma Sa COMBINATION OF RILUZOLE AND GABAPENTINE AND ITS USE AS A MEDICINAL PRODUCT
US6350768B1 (en) 1999-11-24 2002-02-26 Aventis Pharma S.A. Combination of riluzole and of gabapentin and its use as a medicament
US6964982B2 (en) 2000-04-20 2005-11-15 Neurotech Co., Ltd. Compounds, compositions and methods for preventing neurodegeneration in acute and chronic injuries in the central nervous system
IL136687A0 (en) * 2000-06-12 2001-06-14 Mor Research Applic Ltd Pharmaceutical composition for the treatment of multiple sclerosis
US6933310B1 (en) 2000-10-24 2005-08-23 Mitsubishi Pharma Corporation Therapeutic agent for amyotrophic lateral sclerosis (ALS)
WO2002042842A2 (en) * 2000-11-22 2002-05-30 Allergan, Inc. A high-throughput screen for identifying channel blockers that selectively distinguish transient from persistent sodium channels
US6479458B1 (en) 2001-11-08 2002-11-12 Allergan, Inc. Targeting the reverse mode of the Na+/Ca2+ exchanger for the treatment of optic neuropathy associated with glaucoma and ischemic optic neuropathy
US7361478B2 (en) * 2001-11-20 2008-04-22 Allergan, Inc. High-throughput screen for identifying selective persistent sodium channels channel blockers
EP2305252A1 (en) * 2001-12-11 2011-04-06 University Of Virginia Patent Foundation Use of pramipexole to treat amyotrophic lateral sclerosis
EP1551793B1 (en) * 2002-06-19 2016-01-20 AmKor Pharma, Inc. Tetrafluorobenzyl derivatives and pharmaceutical composition for preventing and treating acute and chronic neurodegenerative diseases in central nervous system containing the same
ES2588780T3 (en) * 2002-11-15 2016-11-04 Teva Pharmaceutical Industries Limited Use of rasagiline with or without riluzole for the treatment of amyotrophic lateral sclerosis
JP5006311B2 (en) * 2005-05-25 2012-08-22 チョンワエ ファーマ コーポレーション Substituted tetrafluorobenzylaniline compound and method for producing pharmaceutically acceptable salt thereof
US20070298129A1 (en) * 2005-08-24 2007-12-27 Neurotech Pharmaceuticals Co., Ltd. Compounds and compositions for treating neuronal death or neurological dysfunction
US20070049565A1 (en) * 2005-08-24 2007-03-01 Neurotech Pharmaceuticals Co., Ltd. Combination of cell necrosis inhibitor and lithium for treating neuronal death or neurological dysfunction
CA2661448A1 (en) 2005-08-25 2007-03-01 Steven Michael Weiss Reducing myocardial damage and the incidence of arrhythmia arising from loss, reduction or interruption in coronary blood flow
US8518926B2 (en) 2006-04-10 2013-08-27 Knopp Neurosciences, Inc. Compositions and methods of using (R)-pramipexole
CA2652251A1 (en) 2006-05-16 2007-11-29 Knopp Neurosciences, Inc. Compositions of r(+) and s(-) pramipexole and methods for using the same
AU2007297539A1 (en) * 2006-09-20 2008-03-27 Medivation Neurology, Inc. Methods and compositions for treating amyotrophic lateral sclerosis (ALS)
US8524695B2 (en) 2006-12-14 2013-09-03 Knopp Neurosciences, Inc. Modified release formulations of (6R)-4,5,6,7-tetrahydro-N6-propyl-2,6-benzothiazole-diamine and methods of using the same
WO2008113056A2 (en) 2007-03-14 2008-09-18 Knopp Neurosciences, Inc. Synthesis of chirally purified substituted benzothiazole diamines
KR100852962B1 (en) * 2007-11-12 2008-08-20 주식회사 뉴로테크 Manufacturing method of 2-hydroxy-5-phenylalkylaminobenzoic acid derivatives and their salts
EP2274016B1 (en) * 2008-04-03 2012-07-25 F. Hoffmann-La Roche AG Pegylated igf-i variants for use in the treatment of neuromuscular disorders
US20110190356A1 (en) 2008-08-19 2011-08-04 Knopp Neurosciences Inc. Compositions and Methods of Using (R)- Pramipexole
EP2228054A1 (en) 2009-03-13 2010-09-15 ITALFARMACO S.p.A. Riluzole aqueous suspensions
EP2228055A1 (en) 2009-03-13 2010-09-15 ITALFARMACO S.p.A. Riluzole liquid emulsions
CN102802418A (en) * 2009-06-19 2012-11-28 诺普神经科学股份有限公司 Compositions and methods for treating amyotrophic lateral sclerosis
WO2011074690A1 (en) 2009-12-14 2011-06-23 Kyoto University Pharmaceutical composition for prevention and treatment of amyotrophic lateral sclerosis
US9856210B2 (en) 2010-09-02 2018-01-02 Kyoto University Pharmaceutical composition for prevention and treatment of amyotrophic lateral sclerosis
WO2013096816A1 (en) 2011-12-22 2013-06-27 Biogen Idec Ma Inc. Improved synthesis of amine substituted 4,5,6,7-tetrahydrobenzothiazole compounds
WO2013192610A2 (en) 2012-06-23 2013-12-27 Fox Chase Chemical Diversity Center, Inc. Pro-drugs of riluzole and their method of use for the treatment of amyotrophic lateral sclerosis
CA3132310C (en) 2012-08-07 2024-01-09 Children's Medical Center Corporation Potassium channel openers for treating neurodegenerative diseases
US9662313B2 (en) 2013-02-28 2017-05-30 Knopp Biosciences Llc Compositions and methods for treating amyotrophic lateral sclerosis in responders
CN105764507B (en) 2013-07-12 2019-07-19 诺普生物科学有限责任公司 The level for treating raised eosinophil and/or basophilic granulocyte
US9468630B2 (en) 2013-07-12 2016-10-18 Knopp Biosciences Llc Compositions and methods for treating conditions related to increased eosinophils
ES2813674T3 (en) 2013-08-13 2021-03-24 Knopp Biosciences Llc Compositions and methods for treating plasma cell disorders and b-cell prolymphocytic disorders
ES2871556T3 (en) 2013-08-13 2021-10-29 Knopp Biosciences Llc Compositions and methods for the treatment of chronic urticaria
US20150210679A1 (en) 2014-01-28 2015-07-30 Northwestern University Small molecule inhibitors of superoxide dismutase expression
EP3789027A1 (en) 2015-01-13 2021-03-10 Kyoto University Bosutinib, sunitinib, tivozanib, imatinib, nilotinib, rebastinib or bafetinib for preventing and/or treating amyotrophic lateral sclerosis
US11911369B2 (en) * 2015-03-03 2024-02-27 Biohaven Therapeutics Ltd. Prodrugs of riluzole and their method of use
WO2018093591A1 (en) 2016-11-03 2018-05-24 Juno Therapeutics, Inc. Combination therapy of a cell based therapy and a microglia inhibitor
EP3631468A1 (en) 2017-06-02 2020-04-08 Juno Therapeutics, Inc. Articles of manufacture and methods related to toxicity associated with cell therapy
AU2018275894A1 (en) 2017-06-02 2019-12-12 Juno Therapeutics, Inc. Articles of manufacture and methods for treatment using adoptive cell therapy
EP3644721A1 (en) 2017-06-29 2020-05-06 Juno Therapeutics, Inc. Mouse model for assessing toxicities associated with immunotherapies
US10322114B2 (en) * 2017-07-31 2019-06-18 Above And Beyond Nb, Llc Formulation of a riluzole solution with beta-cyclodextrins
EP3676403A1 (en) 2017-09-01 2020-07-08 Juno Therapeutics, Inc. Gene expression and assessment of risk of developing toxicity following cell therapy
WO2019089848A1 (en) 2017-11-01 2019-05-09 Juno Therapeutics, Inc. Methods associated with tumor burden for assessing response to a cell therapy
JP2022513685A (en) 2018-11-30 2022-02-09 ジュノー セラピューティクス インコーポレイテッド Methods for Treatment with Adoptive Cell Therapy
KR20210110811A (en) 2018-11-30 2021-09-09 주노 쎄러퓨티크스 인코퍼레이티드 Methods of dosing and treatment of B-cell malignancies in adoptive cell therapy
KR20220132527A (en) 2019-12-06 2022-09-30 주노 쎄러퓨티크스 인코퍼레이티드 Methods Related to Toxicity and Responses Associated with Cell Therapy for Treating Cell Malignant Tumors

Family Cites Families (9)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
FR2492258A1 (en) * 1980-10-17 1982-04-23 Pharmindustrie NEW AMINO-2 TRIFLUOROMETHOXY-6 BENZOTHIAZOLE-BASED MEDICINAL PRODUCT
US4826860A (en) * 1987-03-16 1989-05-02 Warner-Lambert Company Substituted 2-aminobenzothiazoles and derivatives useful as cerebrovascular agents
FR2619713B1 (en) * 1987-08-25 1990-08-31 Rhone Poulenc Sante APPLICATION OF AMINO-2 TRIFLUOROMETHOXY-6 BENZOTHIAZOLE TO OBTAIN MEDICINE FOR THE TREATMENT OF SLEEP AND DEPRESSION DISORDERS
US4918090A (en) * 1988-01-25 1990-04-17 Warner-Lambert Company Substituted 2-aminbenzothiazoles and derivatives useful as cerebrovascular agents
US5236940A (en) * 1988-12-15 1993-08-17 Rhone-Poulenc Sante Pharmaceutical compositions, 2-benzothiazolamine derivatives, and their preparation
ES2052954T3 (en) * 1988-12-15 1994-07-16 Rhone Poulenc Sante DERIVATIVES OF IMINO-2-POLIFLUOROALCOXI-6-BENZOTIAZOLE, ITS PREPARATION PROCEDURES AND THE MEDICINES CONTAINING THEM.
FR2649702B1 (en) * 1989-07-13 1991-11-22 Rhone Poulenc Sante ALKYLIMINO-2 BENZOTHIAZOLINE DERIVATIVES, PROCESSES FOR THEIR PREPARATION AND MEDICAMENTS CONTAINING THEM
FR2662160B1 (en) * 1990-05-18 1992-07-24 Rhone Poulenc Sante ALKYLTHIO-3 PROPYL-3 BENZOTHIAZOLINE DERIVATIVES, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM.
FR2663029B1 (en) * 1990-06-07 1992-07-31 Rhone Poulenc Sante BENZOTHIAZOLE DERIVATIVES, THEIR PREPARATION AND THE MEDICINAL PRODUCTS CONTAINING THEM.

Non-Patent Citations (3)

* Cited by examiner, † Cited by third party
Title
Ｊ．Ｎｅｕｒｏｓｃｉ．，第９巻第１１号（１９８９）第３７２０−３７２７頁
Ｎｅｕｒｏｐｈａｒｍａｃｏｌｏｇｙ，第２４巻第８号（１９８５）第７６７−７７３頁
Ｎｅｕｒｏｓｃｉ，Ｌｅｔｔ，第８８巻第２号（１９８８）第１９５−２００頁

Cited By (1)

* Cited by examiner, † Cited by third party
Publication number Priority date Publication date Assignee Title
WO2008010315A1 (en) 2006-07-19 2008-01-24 Nippon Medical School Foundation Therapeutic agent for amyotrophic lateral sclerosis

Also Published As

Publication number Publication date
ES2098558T3 (en) 1997-05-01
FR2688138A1 (en) 1993-09-10
CA2117466C (en) 2000-01-25
KR100190296B1 (en) 1999-06-01
AU666150B2 (en) 1996-02-01
AU2948292A (en) 1993-10-05
SK104794A3 (en) 1995-05-10
NO306534B1 (en) 1999-11-22
MX9206109A (en) 1993-09-01
EP0558861A1 (en) 1993-09-08
HU217130B (en) 1999-11-29
DK0627919T3 (en) 1997-05-12
DE69218255D1 (en) 1997-04-17
SK279046B6 (en) 1998-06-03
EP0627919A1 (en) 1994-12-14
RU2110260C1 (en) 1998-05-10
US5527814A (en) 1996-06-18
GR3022797T3 (en) 1997-06-30
ATE149833T1 (en) 1997-03-15
FR2688138B1 (en) 1995-05-05
RU94041223A (en) 1996-10-20
NO943256L (en) 1994-09-02
HUT70946A (en) 1995-11-28
CZ212094A3 (en) 1994-12-15
NO943256D0 (en) 1994-09-02
CA2117466A1 (en) 1993-09-16
EP0627919B1 (en) 1997-03-12
HU9402558D0 (en) 1994-11-28
JPH07504655A (en) 1995-05-25
ZA928213B (en) 1993-04-30
CZ281293B6 (en) 1996-08-14
UA41879C2 (en) 2001-10-15
DE69218255T2 (en) 1997-09-11
IL103493A (en) 1996-07-23
KR950700060A (en) 1995-01-16
WO1993017683A1 (en) 1993-09-16
IL103493A0 (en) 1993-03-15

Similar Documents

Publication Publication Date Title
JP2713384B2 (en) Use of 2-amino-6- (trifluoromethoxy) -benzothiazole (riluzole) for obtaining a medicament intended for the treatment of motor neuron disease
RU2221563C2 (en) Pharmaceutical composition for treatment of parkinson's disease and parkinson's syndrome, method for its preparing, method for treatment of parkinson's disease and parkinson's syndrome
EP1675591B1 (en) Pharmaceutical composition comprising a monoamine neurotransmitter re-uptake inhibitor and an acetylcholinesterase inhibitor
US5629312A (en) Use of lamotrigine for treating AIDS-related neural disorders
EP2254575B1 (en) Oral l-histidine for the treatment or prevention of atopic dermatitis or contact dermatitis
JP3585045B2 (en) Application of riluzole in the treatment of mitochondrial diseases
TWI224001B (en) Single dose pharmaceutical composition of lasofoxifene for oral administration
JPH0196132A (en) Use of certain compound for treating schizophrenia
JP5078209B2 (en) Use of siamemazine for the treatment of sudden benzodiazepine withdrawal.
HU206623B (en) Process for producing pharmaceutical compositions containing imidazo-pyrrolo-benzodiazepine as antipsychotic active component
GB2083749A (en) Drug combination comprising ambroxol and an antibiotic for the treatment of infectious diseases of the respiratory tract
AU761978B2 (en) Use of 2-amino-6- trifluoromehthoxy- benzothiazole for preventing or treating cerebellum dysfunction
HU226067B1 (en) Pharmaceutical composition containing riluzole and alpha-tocopherol combination and its use
US4225605A (en) Ergolene or ergoline compounds for treating congestive heart failure
HUT71466A (en) Pharmaceutical compositions for inhibition of obsessive-compulsive and consumptive disorders containing 2-phenyl-3-aroyl-benzothiophene-derivatives and process for their preparation
JPS6011422A (en) Antimyodystrophic agent
DE3922387A1 (en) N-BENZYL-N - ((1S, 5S) -6,6-DIMETHYLBICYCLO / 3.1.1 / HEPT-2-YLAETHOXY-AETHYL) -MORPHOLINIUM SALTS CONTAINING GASTROPROTECTIVELY ACTIVE PHARMACEUTICAL PREPARATIONS
WO2021074452A1 (en) Combination preparations of 3-n-formylhydroxylaminopropyl phosphonic acid derivatives or 3-n-acetylhydroxylaminopropyl phosphonic acid derivatives with clindamycin and artesunate
FR2691630A1 (en) Medicaments contg. 5HT antagonists - formulated as anhydrous compsns. for dissolving in water, esp. for migraine treatment

Legal Events

Date Code Title Description
R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

R250 Receipt of annual fees

Free format text: JAPANESE INTERMEDIATE CODE: R250

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20071031

Year of fee payment: 10

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20081031

Year of fee payment: 11

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20091031

Year of fee payment: 12

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20091031

Year of fee payment: 12

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20101031

Year of fee payment: 13

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20111031

Year of fee payment: 14

FPAY Renewal fee payment (event date is renewal date of database)

Free format text: PAYMENT UNTIL: 20121031

Year of fee payment: 15

EXPY Cancellation because of completion of term